Use of dodecanoyl isothiocyanate as building block in synthesis of target benzothiazine, quinazoline, benzothiazole and thiourea derivatives

Article abstract of DOI:10.1515/chempap-2016-0042

Dodecanoyl isothiocyanate (I) reacts additively with anthranilic acid to afford derivatives of thiourea II and benzothiazine III in a one-pot reaction. The cyclisation of thiourea II was achieved using acetic anhydride to form quinazoline derivative IV. The heating of quinazoline IV in acetic anhydride or butan-1-ol gave quinazoline derivatives V or VI, respectively. Benzothiazine III underwent trans-acylation to benzothiazine VII in boiling acetic anhydride. The treatment of IV with hydrazine hydrate, anthranilic acid or ethyl carbazate afforded derivatives of triazoloquinazoline VIII, quinazolinoquinazoline XI or thiosemicarbazide X, respectively. The reaction of I with 2aminophenol or 2-aminothiophenol afforded thiourea derivative XIII or benzothiazole derivative XIV, respectively. Most of the synthesised compounds bear a lauroyl (dodecanoyl) group (a hydrocarbon moiety). The structures of the synthesised compounds were confirmed by microanalytical and spectral data.

Full text of DOI:10.1515/chempap-2016-0042

Chemical Papers 70 (8) 1117–1125 (2016)
DOI: 10.1515/chempap-2016-0042
ORIGINAL PAPER
Use of dodecanoyl isothiocyanate as building block in synthesis
of target benzothiazine, quinazoline, benzothiazole
and thiourea derivatives
Magdy M. Hemdan*, Eman A. El-Bordany
Department of Chemistry, Faculty of Science, Ain Shams University, 11566 Abbasia, Cairo, Egypt
Received 15 August 2015; Revised 7 December 2015; Accepted 16 December 2015
Dodecanoyl isothiocyanate (I) reacts additively with anthranilic acid to afford derivatives of
thiourea II and benzothiazine III in a one-pot reaction. The cyclisation of thiourea II was achieved
using acetic anhydride to form quinazoline derivative IV. The heating of quinazoline IV in acetic
anhydride or butan-1-ol gave quinazoline derivatives V or VI, respectively. Benzothiazine III un-
derwent trans-acylation to benzothiazine VII in boiling acetic anhydride. The treatment of IV with
hydrazine hydrate, anthranilic acid or ethyl carbazate afforded derivatives of triazoloquinazoline
VIII, quinazolinoquinazoline XI or thiosemicarbazide X, respectively. The reaction of I with 2-
aminophenol or 2-aminothiophenol afforded thiourea derivative XIII or benzothiazole derivative
XIV, respectively. Most of the synthesised compounds bear a lauroyl (dodecanoyl) group (a hydro-
carbon moiety). The structures of the synthesised compounds were confirmed by microanalytical
and spectral data.
c
ꢀ 2016 Institute of Chemistry, Slovak Academy of Sciences
Keywords: lauroyl isothiocyanate, thiourea, benzothiazine, quinazoline, thiosemicarbazide deriva-
tives
Introduction
terest in both synthetic and biological fields. Accord-
ingly, methods for the syntheses and modification of
such ring systems continue to be the focus of research
(El-Hiti et al., 2011). Some triazoloquinazolines have
exhibited antibacterial activities (Ghorab et al., 2013).
Further, 3,1-benzothiazine core moieties possess re-
markable potential as anti-radiation agents (Yadav et
al., 2009) and bioactive materials (Simerpreet & Can-
noo, 2013; Gu¨tschow et al., 2012) in addition to their
applications in recording and photographic materials
(Obayashi & Okawa, 2001; Canon, 1984). They are
used in various organic syntheses and transformations
as reaction intermediates (Yadav et al., 2009; Yavari
et al., 2010; Ding et al., 2012). A number of effective
approaches for their preparation have been reported in
the literature (Ding et al., 2013; Gimbert & Vallribera,
2009; Butin et al., 2009). The thiourea backbone also
represents a significant structural motif in pharmaceu-
Many preparatory methods have been reported
for the production of quinazolines (Kidwai et al.,
2007; Barluenga et al., 1994; Raffa et al., 2004).
Quinazolines and their ring-fused derivatives have at-
tracted considerable attention due to the wide spec-
trum of their pharmacological activities such as anti-
inflammatory (Maggio et al., 2001), antimicrobial
(Grover & Kini, 2006) antioxidant (Roopan et al.,
2008), anticancer (Chandrika et al., 2008; Khalil et
al., 2003), antihypertensive (Alagarsamy & Pathak,
2007) antiviral (Schleiss et al., 2008), diuretic (Hayao
et al., 1965; Cohen et al., 1960), antiHIV (Alagarsamy
et al., 2007), anticonvulsants (Laddha & Bhatna-
gar, 2008) and anti-tubercular agents (Mosaad et al.,
2004). Moreover, the chemistry of thioxoquinazolines
has considerable value and has gained increased in-
*Corresponding author, e-mail: mhemdan39@hotmail.com
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M. M. Hemdan, E. A. El-Bordany/Chemical Papers 70 (8) 1117–1125 (2016)
tical agents (Balzarini et al., 2009; Bukvi´c Krajači´c et
al., 2011; Sharma et al., 2010) having antibacterial,
antimalarial, antiviral and anti-tumour activities.
In recent years, the potentials of aroyl isothio-
cyanates (Fahmy et al., 2010; Hemdan, 2010; Hem-
dan et al., 2010; Hemdan & El-Sayed, 2015) and acyl
isothiocyanates (Hemdan et al., 2008, 2012; Hemdan
& Abd El-Mawgoude, 2015a, 2015b) have been ex-
plored in heterocyclic syntheses. In the present in-
vestigation, dodecanoyl isothiocyanate was used as
a building block in the synthesis of quinazoline,
3,1-benzothiazine, benzothiazole and thiourea deriva-
tives. Some of the synthesised target compounds were
substituted by a lauroyl (dodecanoyl) group (a hydro-
carbon moiety) in an attempt to enhance their biolog-
ical activities.
Preparation of 3-dodecanoyl-2-thioxo-2,3-
dihydroquinazolin-4(1H)-one (IV), 3-acetyl-
2-thioxo-2,3-dihydroquinazolin-4(1H)-one
(V) and N-(4-oxo-4H-benzo[d][1,3]thiazin-2-
yl)acetamide (VII)
Compound II (1 g) was refluxed in acetic anhydride
(Ac2O; 10 mL) for 1 h then the solid product was fil-
tered and re-crystallised from EtOH to give colourless
crystals of IV (0.83 g). Similarly, the refluxing of III
or IV (0.5 g) in Ac2O (10 mL) for 3 h afforded VII or
V , respectively. The crystallisation of crude products
from hot EtOH gave yellow crystals of VII (0.23 g)
and colourless crystals of V (0.23 g).
Preparation of 2-thioxo-2,3-dihydroquinazolin-
4(1H)-one (VI), 3-undecyl-[1,2,4]triazolo[3,4-
b]quinazolin-5(10H)-one (VIII), dode-
canehydrazide (IX), 4-dodecanoyl-1-
ethoxycarbonylthiosemicarbazide (X), 6H-
quinazolino[3,2-a]quinazoline-5,12-dione (XI),
1-dodecanoyl-3-(2-hydroxyphenyl)thiourea
(XIII) and N-(benzo[d]thiazol-2-yl)
Experimental
General
All reagents and solvents were purchased from
Merck-Schuchardt (Germany) and used as received;
commercially available solvents (Adwek-Egypt) were
used for crystallisations. Melting points were deter-
mined in open capillary tubes on a Gallenkemp melt-
ing point apparatus and are uncorrected. Elemental
analyses were carried out using a PerkinElmer 2400
CHN elemental analyser. FTIR spectra were recorded
on a PerkinElmer Spectrum RXIFT-IR systems using
dodecanamide (XIV)
Compound IV (1 g) in 10 mL of butan-1-ol was
heated under reflux in the presence of a few drops
of triethylamine for 6 h. The reaction mixture was
concentrated to half its original volume, then cooled
to ambient temperature and the solid product was
filtered and re-crystallised from EtOH to afford VI
as pale yellow crystals (0.37 g). A similar procedure,
with the addition of hydrazine hydrate (3 mmol) or
ethyl carbazate (IUPAC nomenclature: ethoxycarbo-
hydrazide) (3 mmol) or anthranilic acid (3 mmol)
or 2-aminophenol (3 mmol) or 2-aminothiophenol
(3 mmol) and reaction time of 6–9 h (monitored
by TLC) afforded compounds VIII–XIV, respectively.
The following solvents were used for crystallisation:
petroleum ether (60–80◦C) for VIII and X (colourless
crystals); petroleum ether (40–60◦C) for IX (colour-
less crystals); petroleum ether (80–100◦C) for XIII
(colourless crystals) and XIV (pale yellow crystals);
EtOH for XI (colourless crystals).
1
the KBr disc technique. H NMR spectra were mea-
sured in DMSO-d6 on a Varian Gemini 300 MHz in-
strument with TMS as internal standard. Mass spec-
tra were recorded on a Shimadzu GC-MS, QP 1000
EX instrument operating at 70 eV. The reactions and
purity of the products were monitored by thin-layer
chromatography using ethyl acetate/hexane (ϕr = 2 :
1) as the eluent. Merck 60 F254 silica gel TLC plates
(0.2 mm; Darmstadt, Germany) and visualisation by
UV irradiation (254 nm) were used. Dodecanoyl isoth-
iocyanate (I) was prepared following the published
method (El-Bordany, 2012).
Preparation of 2-(3-dodecanoylthioureido)
benzoic acid (II) and N-(4-oxo-4H-3,1-
benzothiazin-2-yl)dodecanamide (III)
Results and discussion
Anthranilic acid (3 mmol) was added to a solution
of isothiocyanate I (3 mmol) in acetonitrile (30 mL)
and the reaction mixture was refluxed for 1 h followed
by cooling to ambient temperature to afford a mix-
ture of II and III as a solid precipitate. This mixture
was suspended in boiling ethanol (2 × 20 mL). The
combined filtrates were cooled to give III as yellow
crystals (0.41 g, 38 %). The residue (0.69 g) was dis-
solved in 50 mL of boiling petroleum ether (80–100◦C)
to give, upon cooling, colourless crystals of II (0.62 g,
55 %).
In the present study, the reactions of dodecanoyl
isothiocyanate (I) with different nucleophiles were in-
vestigated to obtain the target annulated heterocy-
cles of known biological activity. Hence, the inter-
action of equimolar quantities of I with anthranilic
acid in a dry acetonitrile afforded a mixture of 2-(3-
dodecanoylthioureido)benzoic acid (II ) and N-(4-oxo-
4H-3,1-benzothiazin-2-yl)dodecanamide (III ). Heat-
ing of the thiourea derivative II in Ac2O afforded 3-
dodecanoyl-2-thioxo-2,3-dihydroquinazolin-4(1H)-
one (IV) (Fig. 1). Further heating of compound IV in
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1119
Fig. 1. Synthesis of compounds II–VII. Reaction conditions: i) MeCN, reflux; ii) Ac2O, reflux, 1 h; iii) Ac2O; iv) Ac2O, reflux, 3
h; v) butan-1-ol, triethylamine, reflux.
1
Ac2O afforded 3-acetyl-2-thioxo-2,3-dihydroquinazol-
in-4(1H)-one (V ) with a good yield. In addition, 2-
thioxo-2,3-dihydroquinazolin-4(1H)-one (VI ) was ob-
tained upon the heating of compound IV in butan-1-ol
in the presence of a catalytic amount of triethylamine.
On the other hand, N-(4-oxo-4H-benzo[d][1,3]thiazin-
2-yl)acetamide (VII ) was obtained upon the heating
of benzothiazine derivative III in Ac2O (Fig. 1).
The structures of compounds II–VII were con-
firmed from their microanalytical and spectral data.
the H NMR spectrum of III revealed the presence of
two signals for NH protons exchangeable with D2O
(integration ratio of 85 : 15) integrated to one pro-
ton; this observation endorses the existence of com-
pound III in DMSO-d6 as an equilibrium mixture of
tautomers IIIa and IIIb, respectively, in a ratio of ap-
1
proximately 6 : 1 as shown in Fig. 2. The H NMR
spectrum of compound VI revealed two broad singlets
δ 12.66 and 12.42 exchangeable with D2O correspond-
ing to two NH groups. Moreover, an extra signal at δ
4.06 exchangeable with D2O, corresponds to the SH
proton. This confirms the existence of compound VI
in DMSO-d6 solution as thione–thiol tautomers VIa
and VIb in the ratio of 74 : 26 (see Fig. 1). The mass
spectra of the synthesised compounds revealed molec-
ular ion peaks consistent with their proposed struc-
tures. The formation of the derivatives of thiazine III
and quinazoline IV obviously proceeded via the cycli-
sation of thiourea derivative II by removing a molecule
of water. Hence, the thiol tautomer of adduct II con-
The IR spectra showed the absorption frequencies for
1
—
—
—
N—H, C O, C N and C S groups. H NMR spec-
—
—
—
tra displayed signals for aliphatic and aromatic pro-
tons as well as acidic OH, NH and SH protons in the
downfield region that were exchangeable with D2O.
The structure of thiazine derivative III was based on
the relatively high absorption value of the carbonyl
group at 1721 cm−1 and the appearance of the frag-
ment ion at m/z 162 in the mass spectrum corre-
sponding to the benzothiazine moiety. Inspection of
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M. M. Hemdan, E. A. El-Bordany/Chemical Papers 70 (8) 1117–1125 (2016)
Fig. 2. Proposed mechanism for formation of compounds II and III. Reaction conditions: i) Ac2O (loss of water molecule); ii)
MeCN, reflux (loss of water molecule).
Fig. 3. Synthesis of compounds VIII–XI. Reaction conditions: i) hydrazine hydrate, butan-1-ol; ii) anthranilic acid, butan-1-ol,
triethylamine; iii) ethyl carbazate, butan-1-ol, triethylamine.
tributes largely to the formation of compound III; in
addition, compound IV was obtained from the thione
tautomer of compound II as shown in Fig. 2.
[2,3-b]quinazoline-11,13-dione (XII ) is excluded on the
basis of its melting point (m.p. > 300◦C; Butler &
Partridge, 1959; Shestakov et al., 2015). The reaction
was accompanied by the release of gaseous H2S, as
detected by the change in colour to black of a paper
soaked in lead acetate solution.
The treatment of compound IV with hydrazine hy-
drate in butan-1-ol afforded a mixture of 3-undecyl-
[1,2,4]triazolo[3,4-b]quinazolin-5(10H)-one (VIII ), do-
decanehydrazide (IX) and quinazoline VI. A simi-
lar treatment of IV with ethyl carbazate produced
VI as a major product besides a minor amount of
4-dodecanoyl-1-ethoxycarbonylthiosemicarbazide (X)
as depicted in Fig. 3. The heating of quinazoline
IV and anthranilic acid in butan-1-ol under reflux
in the presence of a few drops of triethylamine
afforded 6H-quinazolino[3,2-a]quinazoline-5,12-dione
(XI ). The formation of the isomeric 5H-quinazolino
The IR spectra of compounds VIII–XI showed ab-
—
—
sorption bands corresponding to the N—H and C
O
groups. The 1H NMR spectra exhibited signals charac-
teristic of aromatic and aliphatic protons. In addition,
NH protons exchangeable with D2O were observed in
the downfield region. Inspection of the 1H NMR spec-
trum of VIII revealed its existence as a mixture of
tautomers VIIIa and VIIIb in the ratio of 43 : 57. The
relatively high ratio of VIIIb is in agreement with the
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Table 1. Characterisation data of newly prepared compounds
1121
wi(calc.)/%
wi(found)/%
Yield
%
M.p.
◦C
Compound
Formula
Mr
C
H
N
II
III
C20H30N2O3S
C20H28N2O2S
378.53
360.51
360.51
220.25
178.21
220.25
340.46
214.35
345.50
263.25
350.52
332.50
63.46
63.38
66.63
66.42
66.63
66.29
54.53
54.61
53.92
53.99
54.53
54.28
70.56
70.24
67.24
66.96
55.62
55.47
68.44
68.53
65.10
64.84
68.63
68.36
7.99
7.81
7.83
7.65
7.83
7.71
3.66
3.48
3.39
3.33
3.66
3.44
8.29
8.37
12.23
12.42
9.04
8.77
3.45
3.27
8.63
8.41
8.49
8.23
7.40
7.12
7.77
7.46
7.77
55
38
88
76
76
78
41
26
18
72
76
78
102–104
208–210
153–155
228–230
289–290a
268–270
195–197
104–106b
54–56
IV
C
20H28N2O2S
10H8N2O2S
7.59
V
C
12.72
12.43
15.72
15.65
12.72
12.61
16.46
16.12
13.07
12.76
12.16
11.87
15.96
15.82
7.99
VI
C8H6N2OS
C10H8N2O2S
C20H28N4O
VII
VIII
IX
C
12H26N2O
X
C16H31N3O3S
C15H9N3O2
XI
258–260c
145–147
108–110
XIII
XIV
C19H30N2O2S
C19H28N2OS
7.68
8.42
8.11
a) Leistner et al. (1990) reported m.p. of 304–305◦C; b) El-Sayed and Khairou (2015) reported m.p. of 115–117◦C; c) Butler and
Partridge (1959) reported m.p. of 255–255.5◦C.
Fig. 4. Synthesis of compounds XIII–XIV. Reaction conditions: i) 2-aminophenol, MeCN; ii) 2-aminothiophenol, MeCN (loss of
hydrogen sulfide molecule).
1
aromatic structure of the triazole ring. The H NMR
spectrum of X revealed an extra signal at δ 3.28 corre-
sponding to the SH proton. This suggests the presence
of X in the DMSO-d6 solution as an equilibrium mix-
ture of thione–thiol tautomers Xa and Xb in the ratio
of 46 : 54. The relatively high ratio of thiol from Xb
may be attributed to its stabilisation by the H-bond
butan-1-ol with triethylamine) (Okuda et al., 2010).
The reaction of I with 2-aminophenol and 2-
aminothiophenol was also studied (Uher et al., 1983).
1-Dodecanoyl-3-(2-hydroxyphenyl)thiourea
(XIII )
was obtained upon the treatment of I with 2-amino-
phenol. On the other hand, N-(benzo[d]thiazol-2-
yl)dodecanamide (XIV ) was obtained when I was al-
lowed to react with 2-aminothiophenol (Fig. 4). The
formation of compound XIV was accompanied by the
release of gaseous H2S. The structures of XIII and
XIV were assigned on the basis of the spectral data.
as shown in Fig. 3. The extra signal at δ 152.91 in the
13
—
C NMR spectrum corresponding to the C N group
—
is also supportive of thione–thiol tautomers Xa and
Xb. Moreover, the mass spectral data of compounds
VIII–XI are in accord with their proposed structures
as they show the molecular ion peaks as well as some
important fragmentation peaks. The formation of VIII
and XI can be rationalised on the basis of the cy-
clocondensation of IV with hydrazine molecule or an-
thranilic acid, followed by the expulsion of dodecanoic
acid with the latter. The formation of compound X
is achieved by pyrimidine-ring cleavage under the re-
action conditions (reagent and the high-boiling point
Conclusions
Dodecanoyl isothiocyanate was used in the syn-
thesis of 3,1-benzothiazine, quinazoline, benzothiazole
and thiourea derivatives bearing the dodecanoyl (lau-
royl) group. The lipophilic character of this group (a
hydrocarbon moiety) favours the permeation of these
compounds through lipid barriers in the fungal cell
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M. M. Hemdan, E. A. El-Bordany/Chemical Papers 70 (8) 1117–1125 (2016)
Table 2. Spectral data of newly prepared compounds
Compound
Spectral data
IR, ν˜/cm−1: 3413–2854 (br, O—H), 3242, 3138 (N—H), 3088, 3025 (H—Caryl), 2921, 2852 (H—Calkyl), 1713, 1683
II
—
—
(C O), 1169 (C S), 745 (δ4H, benzene ring)
—
—
1H NMR (DMSO-d6), δ: 0.85 (t, 3H, CH3, J = 6.0 Hz, J = 6.9 Hz), 1.16–1.25 (m, 16H, CH3(CH2)8CH2), 1.54–1.56
(m, 2H, (CH2)8CH2CH2), 2.44 (t, 2H, CH2CO, J = 7.5 Hz, J = 7.2 Hz), 7.34 (t, 1H, J = 7.5 Hz, J = 7.8 Hz),
7.58 (t, 1H, J = 8.1 Hz, J = 7.8 Hz), 7.89 (dd, 1H, J = 2.1 Hz, J = 1.8 Hz), 8.09 (d, 1H, J = 7.8 Hz), 11.33, 12.94
(2brs, each 2H, 2 × NH, exchangeable), 13.30 (brs, 1H, OH, exchangeable)
13C NMR (DMSO-d6), δ: 14.39, 22.53, 24.75, 28.86, 29.13, 29.15, 29.31, 29.42, 29.46, 31.73, 36.15, 125.07, 126.54,
—
—
—
127.82, 130.78, 132.27, 138.41, 167.46 (C O), 174.92 (C O), 179.88 (C S)
—
—
—
MS, m/z (Ir/%): 378 (0) (M+), 371 (0.4), 336 (0.3), 254 (0.7), 241(0.4), 198 (0.6), 183 (0.3), 155 (0.2), 138 (0.7),
128 (2), 114 (2.9), 72 (26), 59 (100)
IR, ν˜/cm−1: 3162 (N—H), 3068 (H—Caryl), 2977, 2925, (H—Calkyl), 1721 (C O), 1630 (C N), 757 (δ4H, benzene
—
—
—
—
III
ring)
1H NMR (DMSO-d6), δ: 0.85 (t, 3H, CH3, J = 6.5 Hz), 1.18–1.24 (m, 16H, CH3(CH2)8CH2), 1.56–1.57 (m, 2H,
(CH2)8CH2CH2), 2.44 (t, 2H, CH2CO, J = 7.4 Hz), 7.43 (t, 1H, J = 7.8 Hz, J = 7.2 Hz), 7.68 (t, 1H, J = 7.2
Hz, J = 7.8 Hz), 7.86 (d, 1H, J = 7.8 Hz), 7.91 (d, 1H, J = 8.4 Hz); for IIIa: 9.54 (brs, 1H, NH, exchangeable); for
IIIb: 8.88 (brs, 1H, NH, exchangeable)
MS, m/z (Ir/%): 360 (0) (M+), 267 (93) ([M.− C6H13
]
+), 261 (22) ([M.− C7H15
]
+), 247 (4) ([M.− C8H17
]
+), 233
(21) ([M.− C9H19
]
+), 219 (27) ([M.− C10H21
]
+), 177 (36) ([M− C11H23CO]+), 162 (100) ([M.− C11H23CONH]+),
146 (28), 134 (26), 120 (56), 90 (49), 77 (31)
IR, ν˜/cm−1: 3228, 3197 (N—H), 3059, 3010 (H—Caryl), 2918, 2848 (H—Calkyl), 1701, (C O), 752 (δ4H, benzene
—
—
IV
ring)
1H NMR (DMSO-d6), δ: 0.84 (t, 3H, CH3, J = 5.4 Hz, J = 6.9 Hz), 1.14–1.23 (m, 16H, CH3(CH2)8CH2), 1.54 (t,
2H, (CH2)8CH2CH2, J = 6.3 Hz), 2.42 (t, 2H, CH2CO, J = 7.5 Hz, J = 7.2 Hz), 7.51 (t, 1H, J = 7.2 Hz, J = 7.5
Hz), 7.59 (d, 1H, J = 7.8 Hz), 7.68 (t, 1H, J = 7.8 Hz, J = 7.5 Hz), 8.04 (d, 1H, J = 7.8 Hz), 11.81 (brs, 1H, NH,
exchangeable)
13C NMR (DMSO-d6), δ: 14.38, 22.52, 24.74, 28.83, 29.07, 29.15, 29.25, 29.41, 31.72, 35.82, 119.85, 124.78, 127.44,
—
—
—
129.31, 136.79, 148.08, 153.39 (C O), 174.23 (C O), 185.03 (C S)
—
—
—
MS, m/z (Ir/%): 360 (44) (M+), 345 (4) ([M.− CH3]+), 331 (28) ([M+.− C2H5]+), 317 (7) ([M.− C3H7]+), 303
(6) ([M.− C4H9]+), 289 (11) ([M.− C5H11
]
+), 275 (8) ([M.− C6H13]+), 261 (4) ([M.− C7H15
]
+), 247 (12) ([M.−
C8H17
]
+), 233 (46) ([M.− C9H19
]
+), 220 (68) ([M.− C10H20
]
+), 205 (14) ([M.− C11H23
]
+), 192 (33), 177 (100),
145 (35), 120 (90), 90 (46), 57 (98)
—
—
V
IR, ν˜/cm−1: 3211, 3197 (N—H), 3062 H—Caryl), 2918 (H—Calkyl), 1700, 1657 (C O), 756 (δ4H, benzene ring)
1H NMR (DMSO-d6), δ:2.14 (s, 3H, CH3CO), 7.52 (t, 1H, J = 7.2 Hz, J = 7.8 Hz), 7.59 (d, 1H, J = 8.4 Hz), 7.87
(t, 1H, J = 7.5 Hz, J = 8.4 Hz), 8.04 (d, 1H, J = 6.3 Hz), 11.88 (brs, 1H, NH, exchangeable)
MS, m/z (Ir/%): 220 (40) (M+), 221 (7) ([M.+ 1]+), 205 (9) ([M.− CH3]+), 192 (23) ([M.− CO]+), 177 (100)
([M.− CHCO]+), 162 (93), 159 (55), 145 (31), 120 (64), 90 (42), 55 (88)
—
—
—
—
VI
IR, ν˜/cm−1: 3218, 3122 (N—H), 3078, 3035 (H—Caryl), 2944 (H—Calkyl), 1690, (C O), 1165 (C S), 761 (δ
,
4H
benzene ring)
1H NMR (DMSO-d6), δ: 4.06 (brs, 1H, SH, exchangeable); 7.51 (t, 1H, J = 7.2 Hz, J = 7.5 Hz), 7.36 (d, 1H, J =
8.1 Hz), 7.72 (t, 1H, J = 8.4 Hz, J = 7.5 Hz), 7.92 (d, 1H, J = 7.8 Hz), 12.42, 12.66 (2brs, each 2H, 2 × NH,
exchangeable)
MS, m/z (Ir/%): 178 (12) (M+), 177 (100) ([M − H]+), 145 (43) ([M − SH]+), 118 (23), 117 (29), 104 (86), 88 (33)
IR, ν˜/cm−1: 3163 (N—H), 3063, 3005 (H—Caryl), 2776 (H—Calkyl), 1657 (C O), 1582 (C N), 765 (δ4H, benzene
—
—
—
—
VII
ring)
1H NMR (DMSO-d6), δ: 2.14 (s, 3H, CH3), 7.51 (t, 1H, J = 7.2 Hz, J = 7.8 Hz), 7.59 (d, 1H, J = 7.8 Hz), 7.87 (t,
1H, J = 7.2 Hz, J = 7.8 Hz), 8.04 (d, 1H, J = 8.4 Hz), 11.83 (brs, 1H, NH, exchangeable)
MS, m/z (Ir/%): 220 (97) (M+), 221 (10) ([M.+ 1]+), 222 (4) ([M.+ 2]+), 205 (8), 192 (6), 178 (100) ([M.−
CH2CO]+), 177 (11) ([M.− CH3CO]+), 162 (97) ([M.− CH3CONH]+), 150 (84), 145 (59), 120 (94), 90 (78), 63
(36)
IR, ν˜/cm−1: 3384, 3281 (N—H), 3046 (H—Caryl), 2951, 2920, 2851 (H—Calkyl) 1714 (C O), 1670, 1652 (C N),
—
—
—
—
VIII
756 (δ4H, benzene ring)
1H NMR (DMSO-d6), δ: 0.84 (t, 3H, CH3, J = 7.2 Hz), 1.22–1.27 (m, 16H, CH3(CH2)8CH2), 1.57–1.60 (m, 2H,
(CH2)8CH2CH2), 2.34 (t, 2H, CH2CO, J = 7.5 Hz), 7.10 (t, 1H, J = 7.8 Hz, J = 6.9 Hz), 7.19 (d, 1H, J = 8.7
Hz), 7.58 (t, 1H, J = 8.4 Hz, J = 7.2 Hz), 7.86 (d, 1H, J = 8.1 Hz), for tautomer VIIIa: 12.32 (brs, 1H, NH,
exchangeable); for tautomer VIIIb: 10.46 (brs, 1H, NH, exchangeable).
13C NMR (DMSO-d6), δ: 14.40, 22.54, 24.80, 29.08, 29.18, 29.29, 29.38, 29.47, 29.48, 31.75, 33.80, 117.13, 121.80,
—
—
—
124.42, 129.94, 134.95, 150.85, 152.85 (C N), 159.87 (C N), 172.82 (C S)
—
—
—
MS, m/z (Ir/%): 340 (47) (M+), 341 (11) ([M.+ 1]+), 325 (4) ([M.− CH3]+), 311 (17) ([M.− C2H5]+), 297 (17)
([M.− C3H7]+), 283 (11) ([M.− C4H9]+), 269 (37) ([M.− C5H11
]
+), 255 (77) ([M.− C6H13
]
+), 241 (16) ([M.−
C7H15
]
+), 227 (21) ([M.− C8H17
]
+), 213 (100) ([M.− C9H19
]
+), 187 (7), 145 (39), 130 (13), 76 (17)
—
—
IX
IR, ν˜/cm−1: 3316, 3292, 3179 (N—H), 2957, 2920, 2850 (H—Calkyl) 1698 (C O)
1H NMR (DMSO-d6), δ: 0.86 (t, 3H, CH3, J = 6.3 Hz, J = 6.9 Hz), 1.24–1.27 (m, 16H, CH3(CH2)8CH2), 1.47–1.49
(m, 2H, (CH2)8CH2CH2), 1.97 (t, 2H, CH2CO, J = 7.2 Hz, J = 7.8 Hz), 4.28 (brs, 2H, NH2, exchangeable), 8.84
(brs, 1H, NH, exchangeable)
MS, m/z (Ir/%): 214 (48) (M+), 200 (18), 183 (100), 176 (73), 165 (23), 145 (56), 123 (87)
Unauthenticated
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M. M. Hemdan, E. A. El-Bordany/Chemical Papers 70 (8) 1117–1125 (2016)
1123
Table 2. (continued)
Compound
Spectral data
—
—
Oamide), 1244
—
X
IR, ν˜/cm−1: 3328, 3288, 3243 (N—H), 2954, 2921, 2851 (H—Calkyl), 1760 (C Oester), 1692 (C
—
—
(C S)
—
1H NMR (DMSO-d6), δ: 0.86 (t, 3H, CH3, J = 5.7 Hz, J = 6.9 Hz), 1.13 (t, 3H, CH3CH2O, J = 5.4 Hz, J = 6.9
Hz), 1.19–1.24 (m, 16H, CH3(CH2)8CH2), 1.47–1.49 (m, 2H, (CH2)8CH2CH2), 2.06 (t, 2H, CH2CO, J = 7.8 Hz,
J = 7.5 Hz), 3.28 (brs, 1H, SH, exchangeable), 4.03 (q, 2H, CH3CH2O, J = 7.8 Hz, J = 6.9 Hz, J = 7.5 Hz), 8.86,
9.49, 13.10 (brs, 3H, 3 × NH, exchangeable)
13C NMR (DMSO-d6), δ: 14.38, 14.95, 22.54, 25.37, 25.43, 26.68, 28.67, 28.93, 28.96, 29.43, 31.73, 33.52, 60.79,
—
—
—
—
152.91 (C N), 156.68 (C O), 166.35 (C O), 172.28 (C S)
—
—
—
—
MS, m/z (Ir/%): 345 (2) (M+), 302 (7) ([M.− C3H7]+), 241 (22) (C11H23CONCS+), 183 (100) (C11H23CO+),
146 (37), 104 (86), 57 (94)
—
—
XI
IR, ν˜/cm−1: 3147 (N—H), 3081, 3043 (H—Caryl), 1713, 1706 (C O), 1628, 1599 (C N), 756 (δ4H, benzene ring)
—
—
1H NMR (DMSO-d6), δ: 7.41 (t, 1H, J = 7.2 Hz, J = 7.5 Hz), 7.48 (d, 1H, J = 8.1 Hz), 7.58 (t, 1H, J = 7.2 Hz,
J = 7.5 Hz), 7.78–7.87 (m, 2H, Haryl), 8.19 (d, 2H, J = 8.1 Hz), 9.20 (d, 1H, J = 9.0 Hz), 12.30 (brs, 1H, NH,
exchangeable)
MS, m/z (Ir/%): 263 (3) (M+), 235 (23), ([M+.− CO]+), 173 (16), 118 (58), 104 (86), 88 (33), 67 (79), 51 (100)
XIII
IR, ν˜/cm−1: 3432 (O—H), 3377, 3213, 3181 (N—H), 3045 (H—Caryl), 2953, 2920, 2850 (H—Calkyl), 1665 (C O),
—
—
—
1185 (C S)
—
1H NMR (DMSO-d6), δ: 0.85 (t, 3H, CH3, J = 6.0 Hz), 1.20–1.25 (m, 16H, CH3(CH2)8CH2), 1.53–1.56 (m, 2H,
(CH2)8CH2CH2), 2.44 (t, 2H, CH2CO, J = 7.8 Hz), 6.80 (t, 1H, J = 7.2 Hz, J = 8.7 Hz), 6.91 (d, 1H, J = 7.8
Hz), 7.04 (t, 1H, J = 8.1 Hz, J = 7.5 Hz), 8.50 (d, 1H, J = 7.8 Hz), 10.12 and 11.27 (2brs, each 2H, 2 × NH,
exchangeable), 12.74 (brs, 1H, OH, exchangeable)
MS, m/z (Ir/%): 350 (1.5) (M+), 333 (0.7), 317 (24), 151 (15), 134 (100), 109 (23), 67 (33)
—
—
XIV
IR, ν˜/cm−1: 3254, 3211 (N—H), 3052 (H—Caryl), 2918, 2851 (H—Calkyl), 1695 (C O), 754 (δ4H, benzene ring)
1H NMR (DMSO-d6), δ: 0.84 (t, 3H, CH3, J = 6.9 Hz, J = 6.3 Hz), 1.23–1.27 (m, 16H, CH3(CH2)8CH2), 1.59–1.64
(m, 2H, (CH2)8CH2CH2), 2.45 (t, 2H, CH2CO, J = 7.2 Hz), 7.29 (t, 1H, J = 7.2 Hz), 7.42 (t, 1H, J = 6.9 Hz),
7.72 (d, 1H, J = 7.8 Hz), 7.95 (d, 1H, J = 7.5 Hz), 12.27 (brs, 1H, NH, exchangeable)
13C NMR (DMSO-d6), δ: 14.38, 22.53, 24.95, 28.93, 29.11, 29.15, 29.29, 29.41, 29.43, 31.71, 35.55, 120.86, 122.07,
—
—
123.84, 126.47, 131.85, 148.97, 158.33(C N), 172.75 (C S)
—
—
MS, m/z (Ir/%): 332 (0) (M+), 311 (34), 258 (43), 234 (60), 167 (43), 148 (37), 63 (46), 51 (100)
membrane, thereby appreciably altering the antimi-
crobial properties of the attached heterocycles (Hem-
dan et al., 2010). Moreover, as the chain-length of the
acyl group is increased, the biological activity could
be improved (Gažák et al., 2010; Hadj Salem et al.,
2010).
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